Peptic ulcers Flashcards
What is a peptic ulcer?
Chronic, usually solitary lesions/sores in areas of GI tract exposed to acid/peptic juices
What are some ulcer symptoms?
Abdominal pain, typically an epigastric burning sensation often occurring nocturnally; pain is caused by acid: duodenal ulcers is relieved by eating, gastric ulcers is caused by eating; nausea, heartburn and bloating
What are some ulcer complications
- penetration: ulcer burrows into the pancreas or liver
- perforation: ulcer opens in the peritoneal cavity- peritonitis
- ulcer erodes into an artery causing upper GI bleeding- vomiting blood
- gastric outlet obstruction due to narrowing of the pyloric canal
What are the factors that cause peptic ulcers to develop?
- helicobacter pylori: primary cause of ulcers of worldwide, causes both duodenal and gastric ulcers
- aspirin and non-steroidal anti-inflammatory drugs: due to role of prostaglandins in mucosal defence, mainly gastric and common in elderly, primary cause of ulcers in high income countries
- idiopathic: could be psychological
- smoking: may act to promote H pylori infection
- Zollinger-Ellison syndrome: rare gastrin-producing tumour of the pancreas or duodenum causing over-secretion of acid
What is helicobacter pylori?
- spiral shaped bacterium causing chronic gastritis
- transmitted by food, contaminated food, saliva; infection typically occurs in childhood and persists indefinitely
- lives in the mucus layer on the surface of epithelial cells
- causes increased secretion of gastrin and pepsin, produces virulence factors which damage the mucosa
- levels of infection and clearance affected by host’s genetic background
- certain strains are especially pathogenic
How do gastric ulcers occur?
- often due to H pylori infection of the gastric corpus
- levels of gastric acid are normal or may be low due to atrophic gastritis
- infection and resulting inflammation reduces gastric mucosal defence
- NSAIDs reduce mucosal defence and cause ulcers by inhibiting gastric mucosal prostaglandin production
What is the pathogenesis of duodenal ulcers?
- due to H pylori infection of the gastric antrum
- somatostatin released by the antrum suppresses the release of gastrin and gastric acid
- H pylori infection of the antrum diminishes somatostatin release causing increase in gastrin and gastric acid release by the corpus
- duodenum is exposed to increased levels of HCl causing gastric metaplasia in the duodenum which can be infected by H pylori, leading to ulceration
How do proton pump inhibitors treat peptic ulcers?
- they irreversibly block parietal cell H+/K+ ATPase
- they are inactive pro-drugs at neutral pH
- they accumulate in the canaliculi and are converted to sulfenamides at pH<3
- these react covalently with suphydryl groups on the H+/K+ ATPase, causing prolonged and >90% inhibition of acid secretion
How do H2 receptor blockers prevent ulcers?
- selectively block parietal cell H2 receptors and reduce acid secretion by ~90%
How does sucralfate prevent ulcers?
- aluminium hydroxide/sulphated sucrose complex
- (-) sulphated sucrose binds to hydrochloric acid and forms a viscous adhesive which binds to (+) groups on proteins in the ulcer crater
- buffers acid and stimulates secretion of mucus, prostaglandin, bicarbonate
- reduces number and adherence of H pylori
- can be used to treat gastric and duodenal ulcers not related to NSAIDs use, also for chronic gastritis and prophylaxis of stress ulcers (ulcers associated with trauma, burns, severe illness)
How can antacids be used to treat ulcers?
- Na+ bicarbonate, Mg2+ carbonate, Al3+ hydroxide
- neutralise gastric acid, inhibiting pepsin action; possible mucosal-protective action
- mainly used initially to control symptoms while waiting for the PPI or H2 blocker to kick in
How does misoprostil prevent ulcers?
- prostaglandins E2 and I2 are important in maintaining the integrity of the gastric mucosa
- their synthesis is inhibited by NSAIDs, increasing the risk of ulcer occurrence
- misoprostil is a stable PGE1 analogue which prevents NSAID-induced damage when taken with the NSAID (not used on its own)
How can anti-microbial therapy be used to prevent ulcers?
- used to eradicate H pylori, prevent ulcer relapse
- usually combined with PPI or an H2 blocker because the PPI has been shown to enhance the antibacterial action
- may be because raising gastric pH stabilises the anti-bacterial drugs
- or because it causes H pylori to grow and synthesise new cell envelope thereby increasing their bactericidal effects
How does bismuth subsalicylate treat ulcers?
- anti-inflammatory due to the salicylate
- stimulation of fluid absorption
- antibacterial actions
- reduces GI motility
- has bactericidal action on H pylori
What treatment should be used on ulcers caused by different factors?
H pylori: antibacterials + PPI or H2 receptor antagonist
NSAID-induced: switch to COX-2 selective NSAID (cardiovascular risk); use misoprostil; PPI for maintenance treatment
Low-dose aspirin: use PPI for maintenance treatment
idiopathic: use PPI for maintenance treatment
